Isoorientin ameliorates lipid accumulation by regulating fat browning in palmitate-exposed 3T3-L1 adipocytes

Stimulation of fat browning using natural bioactive products is regarded as one of the promising approaches to treat obesity and insulin resistance. Here, we investigated the physiological effects of isoorientin on glucose uptake and lipid accumulation in insulin resistant 3T3-L1 adipocytes. To achi...

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Main Authors: Sithandiwe E. Mazibuko-Mbeje, Khanyisani Ziqubu, Phiwayinkosi V. Dludla, Luca Tiano, Sonia Silvestri, Patrick Orlando, Thembeka A. Nyawo, Johan Louw, Abidemi P. Kappo, Christo J.F. Muller
Format: Article
Language:English
Published: Elsevier 2020-06-01
Series:Metabolism Open
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589936820300177
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author Sithandiwe E. Mazibuko-Mbeje
Khanyisani Ziqubu
Phiwayinkosi V. Dludla
Luca Tiano
Sonia Silvestri
Patrick Orlando
Thembeka A. Nyawo
Johan Louw
Abidemi P. Kappo
Christo J.F. Muller
author_facet Sithandiwe E. Mazibuko-Mbeje
Khanyisani Ziqubu
Phiwayinkosi V. Dludla
Luca Tiano
Sonia Silvestri
Patrick Orlando
Thembeka A. Nyawo
Johan Louw
Abidemi P. Kappo
Christo J.F. Muller
author_sort Sithandiwe E. Mazibuko-Mbeje
collection DOAJ
description Stimulation of fat browning using natural bioactive products is regarded as one of the promising approaches to treat obesity and insulin resistance. Here, we investigated the physiological effects of isoorientin on glucose uptake and lipid accumulation in insulin resistant 3T3-L1 adipocytes. To achieve this, 3T3-L1 adipocytes were exposed to 0.75 mM palmitate for 24 h, to induce insulin resistance, before treatment with 10 μM isoorientin or the comparative controls such as CL-316,243 (10 μM), pioglitazone (10 μM) and compound C (1 μM) for 4 h. Relevant bioassays and Western blot analysis were conducted on these insulin resistant cells. Our results showed that palmitate exposure could induce insulin resistance and mitochondrial dysfunction as measured by reduction in glucose uptake and impaired mitochondrial bioenergetics parameters. However, treatment with isoorientin reversed these effects by improving glucose uptake, blocking lipid accumulation, and modulating the process of mitochondrial respiration. Mechanistically, isoorientin could mediate lipid metabolism by activating 5′ AMP-activated protein kinase (AMPK), while also effectively modulating the expression of genes involved in fat browning such as peroxisome proliferator-activated receptor gamma (PPAR)γ/α and uncoupling protein 1 (UCP1). In conclusion, isoorientin impacts insulin resistance in vitro by improving glucose uptake and mitochondrial function, consistent to modulating the expression of genes involved in energy metabolism and fat browning.
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spelling doaj.art-16153e8cdfdf4f459f9bf3abce29c3e72022-12-21T20:22:09ZengElsevierMetabolism Open2589-93682020-06-016100037Isoorientin ameliorates lipid accumulation by regulating fat browning in palmitate-exposed 3T3-L1 adipocytesSithandiwe E. Mazibuko-Mbeje0Khanyisani Ziqubu1Phiwayinkosi V. Dludla2Luca Tiano3Sonia Silvestri4Patrick Orlando5Thembeka A. Nyawo6Johan Louw7Abidemi P. Kappo8Christo J.F. Muller9Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, 7505, South Africa; Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa; Department of Biochemistry, Faculty of Natural and Agricultural Sciences, North West University, Mafikeng Campus, Mmabatho, 2735, South Africa; Corresponding author. Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, 7505, South Africa.Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, 7505, South Africa; Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, 3886, South AfricaBiomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, 7505, South Africa; Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona 60131, ItalyDepartment of Life and Environmental Sciences, Polytechnic University of Marche, Ancona 60131, ItalyDepartment of Life and Environmental Sciences, Polytechnic University of Marche, Ancona 60131, ItalyDepartment of Life and Environmental Sciences, Polytechnic University of Marche, Ancona 60131, ItalyBiomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, 7505, South Africa; Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, 7505, South AfricaBiomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, 7505, South Africa; Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, 3886, South AfricaDepartment of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, 3886, South Africa; Department of Biochemistry, Faculty of Science, University of Johannesburg, Kingsway Campus, Auckland Park, 2006, South AfricaBiomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, 7505, South Africa; Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa; Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, 3886, South AfricaStimulation of fat browning using natural bioactive products is regarded as one of the promising approaches to treat obesity and insulin resistance. Here, we investigated the physiological effects of isoorientin on glucose uptake and lipid accumulation in insulin resistant 3T3-L1 adipocytes. To achieve this, 3T3-L1 adipocytes were exposed to 0.75 mM palmitate for 24 h, to induce insulin resistance, before treatment with 10 μM isoorientin or the comparative controls such as CL-316,243 (10 μM), pioglitazone (10 μM) and compound C (1 μM) for 4 h. Relevant bioassays and Western blot analysis were conducted on these insulin resistant cells. Our results showed that palmitate exposure could induce insulin resistance and mitochondrial dysfunction as measured by reduction in glucose uptake and impaired mitochondrial bioenergetics parameters. However, treatment with isoorientin reversed these effects by improving glucose uptake, blocking lipid accumulation, and modulating the process of mitochondrial respiration. Mechanistically, isoorientin could mediate lipid metabolism by activating 5′ AMP-activated protein kinase (AMPK), while also effectively modulating the expression of genes involved in fat browning such as peroxisome proliferator-activated receptor gamma (PPAR)γ/α and uncoupling protein 1 (UCP1). In conclusion, isoorientin impacts insulin resistance in vitro by improving glucose uptake and mitochondrial function, consistent to modulating the expression of genes involved in energy metabolism and fat browning.http://www.sciencedirect.com/science/article/pii/S2589936820300177IsoorientinInsulin resistanceLipid accumulationFat browning3T3-L1 adipocytes
spellingShingle Sithandiwe E. Mazibuko-Mbeje
Khanyisani Ziqubu
Phiwayinkosi V. Dludla
Luca Tiano
Sonia Silvestri
Patrick Orlando
Thembeka A. Nyawo
Johan Louw
Abidemi P. Kappo
Christo J.F. Muller
Isoorientin ameliorates lipid accumulation by regulating fat browning in palmitate-exposed 3T3-L1 adipocytes
Metabolism Open
Isoorientin
Insulin resistance
Lipid accumulation
Fat browning
3T3-L1 adipocytes
title Isoorientin ameliorates lipid accumulation by regulating fat browning in palmitate-exposed 3T3-L1 adipocytes
title_full Isoorientin ameliorates lipid accumulation by regulating fat browning in palmitate-exposed 3T3-L1 adipocytes
title_fullStr Isoorientin ameliorates lipid accumulation by regulating fat browning in palmitate-exposed 3T3-L1 adipocytes
title_full_unstemmed Isoorientin ameliorates lipid accumulation by regulating fat browning in palmitate-exposed 3T3-L1 adipocytes
title_short Isoorientin ameliorates lipid accumulation by regulating fat browning in palmitate-exposed 3T3-L1 adipocytes
title_sort isoorientin ameliorates lipid accumulation by regulating fat browning in palmitate exposed 3t3 l1 adipocytes
topic Isoorientin
Insulin resistance
Lipid accumulation
Fat browning
3T3-L1 adipocytes
url http://www.sciencedirect.com/science/article/pii/S2589936820300177
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